Indicative operational, financial and environmental impact of Thiomersal-free vaccines

Transcription

1 Indicative operational, financial and environmental impact of Thiomersal-free vaccines Anthony Battersby & Andrew Garnett FBA Health Systems Analysts 18 th April

2 Methodology Questionnaire sent to 35 vaccine manufacturers: 23 of 35 WHO-prequalified manufacturers responded. (66% response) WHO questionnaire on thiomersal-containing vaccines February 2012 If YES, please list these preservative options Preservative Manufacturer: Respondent: address for correspondence: 5 Would phenoxyethanol or another preservative give the same shelf life as the thiomersal? If NO, please comment on likely shelf life: 1 Please list all your vaccine and presentation combinations which currently contain thiomersal. Include any products made by subsidiary companies. Insert additional rows if needed. Product Presentation. Choose from list, or specify alternative Quantity produced in 2011 (doses) Price per dose 2011 (USD) 6 Are there any other techniques, such as physical barriers which could allow preservative-free multi-dose vials to be used safely in accordance with the existing WHO multi-dose vial policy? 2 Do you manufacture thiomersal-free versions of any vaccines and sera listed above? 7 What would be the likely development cost of replacing thiomersal with another preservative or barrier device? If YES, please complete the following table. Insert additional rows if needed. Product Presentation. Choose from list, or specify alternative Quantity produced in 2011 (doses) Price per dose 2011 (USD) 8 Alternatively, what would be the likely development cost of introducting a preservative-free range of vaccines? 3 Could any of your current range of vaccines use Phenoxyethanol instead of Thiomersal? If YES, please list these products Product 4 Are there any other mercury-free preservatives that you could use? 9 How long would it require for you to be able to apply for a licence for vaccines without thiomersal? 10 How long would re-licencing take? 11 What would be the likely affect be on the cost of the vaccine (percent increase or decrease) 18 th April

3 Methodology Discussions with vaccine and Thiomersal manufacturers Modelling based on PAHO-UNICEF 2011 procurement quantities and world data extrapolated from State of the World s Children 2011 Case study based on one country data Infrastructure costs from PQS, cold room manufacturer and other sources PQS Performance, Quality & Safety 18 th April

4 World production of Thiomersal 1 manufacturer of pharmaceutical grade Thiomersal? 1993:10,000Kg 2011: 2,434Kg ointments & creams, pertussis and 0.3% eye drops, 2.8% influenza, 8% animal vaccines, 36.0% human vaccines, 52.0% 18 th April

5 Vulnerabilities Single manufacturer of pharmaceutical grade Thiomersal. Declining market for Thiomersal One year s assured stock of Thiomersal Basle Convention on movement of hazardous waste may prevent movement of raw material (mercuric chloride) In 2012 UNICEF has interruptions in supply for DPT, YF, PCV & RV. 18 th April

6 Development COSTS to go Thiomersal-free Clinical trials and licencing, 16 pre-qualified manufacturers and 67 vaccines, indicative cost of at least $1,000,000 per vaccine Expansion of production plant, additional land, high speed filling, cost unknown, indicated cost millions of $ Assurance and/or soft loans will be required from purchasers before manufacturers will commit. Market uncertainty may cause smaller vaccine manufacturers to stop production of Thiomersalcontaining vaccines 18 th April

7 Development TIME to go Thiomersal-free Clinical trials may take 2-5 years Licencing may take 1-2 years for an individual manufacturer and 4-5 years for world-wide coverage Full expansion of manufacturing capacity probably will not take place until trials are completed and may take 1-2 years WHO pre-qualification cannot take place until vaccines are licenced Complete transition may take 10 years or more Transition will inevitably result in some eventual redundancy which will have to be paid for, because existing Thiomersal lines will be needed during transition 18 th April

8 Cost implications of removing Thiomersal Price per dose for Thiomersal-free $6.0 US$/dose 600% $ % $ % $ % $ % $ % $0.0 0% TT (20) TT (10) DT Adult (10) DT Adult (10) DT Paed.(10) DT Paed.(10) DPT(20) DPT(10) Hep. B Adult(1) Hep. B Paed.(10) Hep. B Adult(10) Hep.B Adult(10) Hep. B Paedi (1) Hep. B Paed.(1) Hep. B Paed.(2) Hep. B Paed.(6) Hep.B Adult(1) Hep. Adult(1) Hep. B Adult(1) Mening.l A Conj.(10) flu (Nh) Trival.P.(20) Penta. Lyoph(10) Penta. Lyoph(2) DPT+Act-Hib Lyo.(1) Penta. Lyoph(1) Penta fully liquid (1) DPT+Act-Hib Lyo.(1) DPT-Hib Liquid(10) flu (Nh) Trival. A.(10) PAHO & UNICEF2011 Thiomersal free % change 18 th April

9 Cost implications of removing Thiomersal Proportional breakdown of cost per vial for expensive vaccines increase for removing thiomersal 1 vial 2 VVM label and printing 3 increase for handling single dose 3 vaccine Range $ $25 per dose 1. Data from manufacturer 2. Average of PAHO/UNICEF 2011 mix 3. Data from manufacturers 18 th April

10 Cost implications of removing Thiomersal Proportional breakdown of cost per vial for cheapest vaccines increase for removing thiomersal 1 increase for handling single dose 3 vaccine VVM label and printing 3 vial 2 1. Data from manufacturer 2. Minimum of PAHO UNICEF 2011 mix 3. Data from manufacturers 18 th April

11 Cost implications of change: global PAHO/UNICEF 2011 supply. Existing total v Thiomersal-free equivalent 800 US$ (millions) 700 $ $522 31% increase PAHO & UNICEF 2011 PAHO & UNICEF 2011 T-free 18 th April

12 Cost implications of change: global 1,200 1, PAHO/UNICEF US$ (millions) effective cost, allowing for wastage 64% increase over PAHO/UNICEF 2011 $ % increase $1, All single dose 10% wastage MDVP with discard after 6hrs.(40% wastage) 10% wastage on single dose presentation because in-country studies indicate that 5% is not enough 18 th April 2012 Includes 65.5million Penta with trace of Thiomersal in the pertussis 12

13 Cost implications of change: global PAHO/UNICEF supply of DPT-containing vaccine extended to the rest of the world US$ (millions) 1,600 1,400 $1,379 1,200 1, $ % increase PAHO & UNICEF 2011: DPTcontaining World: DPT-containing 18 th April

14 Cost implications of change: global World: Influenza vaccine $10,000 $9,000 $8,000 $7,000 $6,000 $5,000 $4,000 $3,000 $2,000 $1,000 $0 US$(millions) $5,475 31% increase $7,195 64% increase $8,993 Flu 2011 Flu T-free Flu T-free 25% loss Based on: PAHO price of $3.7 per dose in 10 dose vials 1.5 billion doses annually. Source: manufacturer 18 th April

15 Cost implications of change: Country A 25 US$(millions) % increase % increase 0 Penta,DPT,HepB TT (20d.) Total 2011 prices Thiomersal-free prices 18 th April

16 Cost implications Country A example Total Annual Vaccine Cost 60,000,000 US $ 50,000,000 40,000,000 30,000,000 20,000,000 10,000,000 0 Existing Vaccines 2011 T-free vaccines 18 th April

17 Cost implications Country A example Total Annual Shipping Cost 1,400,000 1,200,000 1,000, , , , ,000 0 US $ Existing Vaccines 2011 T-free vaccines 18 th April

18 Cost implications Country A example Total Annual Landed Cost 60,000,000 US $ 50,000,000 40,000,000 30,000,000 20,000,000 10,000,000 0 Existing Vaccines 2011 T-free vaccines 18 th April

19 Volume implications - global Based on PAHO-UNICEF 2011 procurement: compared with total volume for 2011 mix Range of single dose vial sizes 9.7 cm³ to 40.1 cm³ * Maximum volume-per-dose for current single dose: +324% Minimum vial size (all 9.7 cm³ per dose): +165% Impact on cold chain equipment: Example from Country A : indicative estimate $1,032,000 of additional equipment and the buildings to house that equipment * Source of vaccine volume data: Optimize packaging study 18 th April

20 Volume implications Country B example Country B FIB volume analysis: Schedule without NUVI Vollume per Fully Immunized Beneficiary(cm3) % + 6% +5.5% Primary, Sub-national Lowest Delivery Service Point 2011-max 2011-max 01-d Supply chain level NUVI=New and Underutilised Vaccine Introduction 18 th April

21 Volume implications Country A example Country A FIB volume analysis: Schedule without NUVI Volume per Fully Immunized Beneficiary (cm3) % +264% +247% 2011-max 2011-max 01-d 0 Primary, Sub-national Lowest Delivery Service Point Supply chain level NUVI=New and Underutilised Vaccine Introduction 18 th April

22 International air shipment implications Source: Boeing based on hold capacity data for passenger aircraft 2010 Guidelines to Defra / DECC s GHG Conversion Factors for Company Reporting: Methodology Paper for Emission Factors 18 th April

23 International air shipment implications Source: Boeing based on hold capacity data for passenger aircraft 2010 Guidelines to Defra / DECC s GHG Conversion Factors for Company Reporting: Methodology Paper for Emission Factors 57 GAVI countries 590 tonnes CO 2 e 282% increase Country A Annual Shipping Cost 1,400,000 1,200,000 1,000, , , ,000 US $ $758,625 $387,532 $1,146, ,000 0 Existing Vaccines 2011 T-free vaccines 18 th April

24 Workload implications Increased workload with single-dose vials: For storekeepers having to manage much larger volumes. For nurses with larger session sizes, additional staff may be required? For supervisors and trainers Health workers and storekeepers will need training in management and use of smaller presentations. Time taken to administer 30 injections (seconds) Difference from presentation vaccinator 1 vaccinator 2 vaccinator 3 vaccinator 4 average using 10 dose 1 dose 1,016 1, ,167 1,167 38% slower 2 dose % slower 10 dose , % Uniject TM % faster Source: Lorenson K, Kristensen D. Time and Motion Study with Potential Human Papillomavirus (HPV) Vaccine Product Presentations. Seattle: PATH; th April

25 Workload implications Carrying vaccines during collections and outreach: Larger capacity or multiple vaccine carriers will be needed for routine outreach. Volume and weight become an issue. For country A ~ 4,000 additional vaccine carriers Administered doses gross vol of Vaccine Carriers Outreach target pop WCBA Penta TT all other vax visit /yr existing doses incl waste new doses incl waste existing pres.cc 3 new pres.cc 3 existing vol Lt. new vol Lt. Nbr. Of Weight 1.7lt VC (Kg.) A , B But it is not only vaccines that have to be carried: 18 th April

26 Workload implications 18th April 2012 Existing outreachload load T-free outreach 26

27 Outreach operations Can preservative-free vaccines safely be used outside the cold chain for: Extended outreach? Birth-dose HepB? Campaigns - e.g. Meningococcal A (MenAfriVac ) 300 million people by 2015 stability and safety profiles need to be assessed 18 th April

28 Waste management implications Based on 2011 PAHO-UNICEF procurement data: 7,600m 3 Current discarded vaccine vials contain ~ 9 kg Hg Discarded syringes from 2011 contain ~ 0.25 kg Hg (~ 275 million syringes) With single-dose vials, vial waste would increase from 2,350 m³ to between 3,850 m³ and 7,600 m³ 2,350m 3 3,850m 3 18 th April

29 Waste management implications Based on 2011 PAHO-UNICEF procurement data: if Thiomersal is retained what happens if US-type legislation is extended globally? 18 th April

30 Harmonising vial sizes and packaging Define target product profiles: Minimum possible vial sizes Compatibility with high-speed filling machines Dimensionally coordinated primary, secondary and tertiary packaging Good ergonomic design Continued ability to carry out shake test Clear and consistent labelling Allow space for future bar coding Minimum airfreight weights and volumes* *Current insulated shipping container weights per dose for single-dose vial presentations range from 10.0 grams for a single-dose HepB vaccine up to 41.0 grams for a 2 vial pentavalent liquid-lyo vaccine 18 th April

31 Initial conclusions Removal of Thiomersal will result in: Major impact on vaccine manufacturing. Higher international and national distribution costs. Higher carbon emissions Higher vaccine costs Greater workload for both logistic and nursing staff Greater volume of waste A transition period of up to 10 years to complete clinical trials, obtain licences & WHO pre-qualification, retool vaccine production plants, upgrade in-country cold chains and recruit and retrain staff. Countries may begin to question the cost-benefit of immunisation 18 th April

32 Initial conclusions If Thiomersal removal is implemented: There is high risk of serious programme disruption, brought about by demand for Thiomersal-free vaccine before it is available, and during the transition. (Already raised at INC3) The cost changes will require a re-examination of the relative cost-effectiveness of immunisation as a public health intervention and countries will have to reassess where to invest their scarce health resources. A consultative body will need to be established to reach agreement on: the transition programme, enable financing, identify detailed operations research, coordinate production, explain the transitional arrangements and obtain buy-in by all stakeholders. 18 th April

33 Further detailed study is needed to support a definitive decision. Whatever that decision is, there will have to be major advocacy to ensure that all parties support the decision. This is all to do with the balance of risk - what will achieve the greatest good for the most people? Removing this molecule from all vaccines will be very disruptive, time consuming and expensive 18 th April

34 Questions not yet completely quantified Is there only a single manufacturer of pharmaceutical grade Thiomersal? How vulnerable is that manufacturer? Does the Basle Convention on movement of hazardous waste prevent movement of raw material (mercuric chloride)? What are the cost implications for manufacturers? 18 th April